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Award Ceremony Speech

During the 19th century, the association between disease symptoms
and organ damage was well understood. Trouble with urine could be
caused by damage of the kidney, and if the skin was yellow the
cause could be in the liver. Damage to the kidney was most often
incurable. Therefore, it was thought very early that perhaps a
new undamaged organ from somebody else could cure the disease.
Thus, at the turn of the century many heroic attempts were made
to transplant kidneys from swine, sheep and goats, however
without success. In 1902, attempts were made to transplant a
kidney from one human being to another, again with no success.
Very soon it was discovered that it was possible to transplant an
organ or tissue within an individual without harm, but not
between individuals. In 1912, Alexis Carrel received
the Nobel Prize among other things for his discoveries concerning
transplants of blood vessels and organs. However, this success
was limited to transplants within an individual. Carrel concluded
that there was a biological force that prevented transplantation
between individuals, and he believed that it would never be
possible to succeed in having an organ from one individual
function in another. He received support for his belief from
among others, the 1960 Nobel Prize-Winner, Peter Medawar, who
discovered the role of the immune defence system in rejection of
a graft and also showed that the biological force defined by
Carrel was of an immunological nature.

Joseph Murray was not discouraged by this
knowledge. There were reasons to believe that the immunological
barrier was lacking between identical twins. Joseph Murray
developed a surgical technique for kidney transplantation in dogs
and showed that a kidney that was transplanted from one dog to
the other could be induced to function. He used the technique in
the first successful kidney transplant between identical twins in
December 1954. Richard Herrick, who had incurable kidney damage
was the first candidate. In order to make sure that he and his
brother Ronald were identical twins, Joseph Murray asked the
police in Boston to document their fingerprint patterns. During a
routine review of police records, journalists found out about the
investigation and its confidentiality was breached. However,
Richard Herrick appeared to take this leakage to the press
calmly. He became the darling of the media. The operation worked
out perfectly and the kidney functioned well. Richard Herrick
married his recovery-room nurse and became the father of two
children. He lived happily for eight years when he died of a
heart infarction. Joseph Murray later performed several other
transplants between identical twins. However, most patients with
incurable kidney damage had no twins, and it was therefore some
time before such patients could become transplant candidates.

About two years later Donnall Thomas
attempted to use bone marrow transplantation to cure terminal
cancer patients, most of them with leukemias or cancers involving
the bone marrow. He first treated the patients with
bone-marrow-ablative total body irradiation. The goal was to cure
the patients from the cancer disorder and to kill the bone marrow
cells. Donnall Thomas showed that it was possible to remove about
one liter of bone marrow out of the bones of a healthy
individual. It was possible to give this marrow to the cancer
patient by infusing it into a blood vessel. The bone marrow cells
found the right spots in the new body where they could produce
new normal and functioning blood cells, which soon appeared in
the circulatory system. However, the healthy marrow also
contained the defense cells, and these attacked their new host.
The result was unfortunately a reversed and deadly rejection
reaction called the graft-versus-host-reaction.

During the 1950s and 1960s some discoveries
were made that were of the utmost importance for future successes
in transplantation research. Jean Dausset discovered
human transplantation antigens, a kind of fingerprints of the
cells in the body. He was rewarded for this discovery with the
Nobel Prize in 1980. About the same time George Hitchings and
Gertrud Elion discovered the first cytotoxic drugs for which
they were awarded the Nobel Prize in 1988. These cytotoxic drugs
could also diminish the rejection reaction. Joseph Murray first
used total body irradiation in attempts to prevent this reaction.
Later he and others showed that azathioprin, one of the drugs
discovered by Hitchings and Elion, was the most effective of
these drugs in preventing rejection. This led to the first
successful kidney transplantation between relatives that were not
identical twins, and also to the first successful transplantation
using kidneys from deceased persons. The best results were
obtained when donors were selected who matched the patient's
transplantation antigens. Kidney and organ transplantation was
established as a treatment method. Today about 20,000 kidneys are
transplanted every year, and more than 100,000 patients have
gained a new and better life after transplantation.

Donnall Thomas managed to diminish the
graft-versus-host reaction using the cytotoxic drug methotrexate.
He showed very soon that if a donor, usually a sibling, was
selected by typing for transplantation antigens, it was possible
to cure leukemia, certain inherited disorders of the bone marrow,
and the severe blood disorders, aplastic anemia and thalassemia.
More than 10,000 patients have been cured, or have been given a
normal life, with the help of bone marrow transplantation.

Dr. Joseph Murray and Dr. Donnall
Thomas,

On behalf of the Nobel Assembly of the Karolinska Institute I
would like to congratulate you on your outstanding
accomplishments and ask you to receive the Nobel Prize in
Physiology or Medicine from the hands of His Majesty the
King.